Preparation of high molecular weight polysuccinimides

ABSTRACT

Described are methods of production of polysuccinimides having molecular weights up to 200,000 daltons and higher. The polysuccinimides of the invention are essentially unbranched and uncrosslinked. They can be modified by crosslinking, ring-opening, and/or other functionalization, if desired, to form gelling materials of superior performance. The high Mw polysuccinimides are also particularly useful as thickening agents, viscosity modifiers, emollients, humectants and in other applications that are known in the art to be serviced most effectively by molecules of higher molecular weight.

This patent application is a continuation of U.S. patent applicationSer. No. 10/630,585 filed on Jul. 29, 2003, which claims priority toU.S. Provisional Patent Application No. 60/400,663 filed on Aug. 2,2002, both of which are incorporated herein in their entirety byreference.

FIELD OF THE INVENTION

The present invention relates to a method of production ofpolysuccinimides, and in particular to production of polysuccinimideswhich are essentially unbranched and have molecular weights up to200,000 daltons and higher.

REFERENCES

Adler, D. E., M. B. Freeman, J. M. Lipovsky, and Y. H. Paik. 1995. Acidcatalyzed process for preparing amino acid polymers. U.S. Pat. No.5,457,176.

Batzel, D. A., J. F. Kneller, and A. R. Y. Meah. 1996. Production of apolysuccinimide and derivatives thereof in the presence of asulfur-containing dehydrating agent. U.S. Pat. No. 5,508,434.

Chou, Y. 1999. Process for production of polysuccinimide. U.S. Pat. No.5,856,427.

Fox, S. W. and K. Harada. 1962. Thermal polymerization of amino acidmixtures containing aspaitic acid or a thermal precursor of asparticacid. U.S. Pat. No. 3,052,655.

Jacquet, B., C. Papantoniou, G. Land, S. Forestier, and C. Souilly.1982. Polyaspaitic acid derivatives, their preparation and their use incosmetic composition. U.S. Pat. No. 4,363,797.

Irizato, Y., C. Higuchi, T. Ishitoku, K. Takuma, and K. Machida. 2001.Manufacture of polysuccinimides for use as precursor or intermediate inmanufacture of polyaspaitic acid. JP Kokai No. 2001-302794.

Kalota, D. J. and D. A. Martin. 1994. Preparation of polysuccinimide.U.S. Pat. No. 5,329,020.

Kato, T., M. Sukegawa, Y. Irizato, and H. Tamatani. 1999. Manufacture ofpolysuccinic acid imide used as intermediates for pharmaceuticals andcosmetics. JP Kokai No. 11-240947.

Kato, T., M. Sukekawa, Y. Irizato, and H. Tamatani. 2000. Manufacture ofpolysuccinic acid imide. JP Kokai No. 2000-169577.

Knebel, J. and K. Lehmann. 1992. Method of increasing the molecularweight in the manufacture of polysuccinimide. U.S. Pat. No. 5,142,062.

Mazo, G. Y., R. J. Ross, J. F. Kneller, and J. Mazo. 2001. Production ofsuccinimide copolymers in cyclic carbonate solvent. U.S. Pat. No.6,197,897.

Nagatomo, A., H. Tamatani, M. Ajioka, and A. Yamaguchi. 1996.Preparation process of polysuccinimide. U.S. Pat. No. 5,484,945.

Neri, P., G. Antoni, F. Benvenuti, F. Cocola, and G. Gazzei. 1973.Synthesis of α,β-poly[(2-hydroxyethyl)-DL-aspaitamide], a new plasmaexpander. J Med. Chem. 16:893-897.

Ross, R. J., K. C. Low, and L. P. Koskan. 1996. Soluble, crosslinkedpolyaspartates U.S. Pat. No. 5,552,516.

Sikes, C. S. 1999. Imide-free and mixed amide/imide synthesis ofpolyaspartate. U.S. Pat. No. 5,981,691.

Sikes, C. S. 2002. Copolymers of amino acids and methods of theirproduction. PCT Appn. Serial No. US03/14312.

Sikes, C. S., Ringsdorf, L. and Swift, G. 2002. Comonomer compositionsfor production of imide-containing polyamino acids. U.S. Pat. No.6,495,658.

Tang, J. 1999. Biodegradable poly(amino acid)s, derivatized amino acidpolymers and methods for making same. U.S. Pat. No. 5,929,198.

Wang, Y. 2000. Direct polyaspartate synthesizing process catalyzed byaspartic acid precursor. Chinese Patent No. 1267673.

Uenaka, M., S. Koshigaya-shi, and M. Tomida. 1977. Process for producingpolysuccinimides and use of said compound. European Patent Application,EP 0791616 A1.

BACKGROUND OF THE INVENTION

Thermal polycondensation of aspartic acid and aspartic acid precursors,such as maleic acid plus ammonia, to produce polysuccinimide, which isthen converted to polyaspartate by mild alkaline hydrolysis (see schemebelow), has been the subject of commercial research and development formore than two decades. Much of this effort is summarized in U.S. Pat.Nos. 5,981,691 and 6,495,658 to Sikes and coworkers (1999, 2002) and incopending U.S. application Ser. No. 10/431,124 (PCT Appn. Serial No.US03/14312) by Sikes, which are incorporated herein by reference.

Generally, the polyaspartates formed by polysuccinimide ring openingcomprise both D- and L-aspartate residues, and have amide linkagesthrough both the α and β carboxylic groups, as shown, regardless of thestereochemistry of the aspartic acid (or aspartic acid precursor)monomers.

The principal commercial routes to polysuccinimides and polyaspartatesnow in use include the maleic acid/ammonia method and direct thermalconversion of aspartic acid monomer, as discussed in theabove-referenced cases. These routes generate molecules of relativelylow molecular weight (several thousand daltons), often havingsignificant branching (branch points as frequent or more frequently asevery tenth residue on average) and often ranging in color from lighttan to a darker reddish color. Such molecules have been commercializedin specialty detergents and as environmentally friendly oilfieldadditives. However, many if not most markets often require or at leastfavor higher molecular weight polymers, if available.

Methods for preparing higher molecular weight polysuccinimides via acidcatalysis have been developed. See, for example, Fox and Harada, 1962,U.S. Pat. No. 3,052,655; Neri et al., J. Med. Chem. 16, 893-897 (1973).The catalysts are typically phosphoric acid or polyphosphoric acid,employed at up to 50-65% by weight, relative to the aspartic acidmonomer. In general, an admixture or paste of aspartic acid (powder orcrystal) with the phosphoric catalyst is formed, then thermallypolymerized, e.g. at 200° C. for 2-4 hours, to produce thepolysuccinimide. Molecules in the range of 30,000 and somewhat higherare readily achievable via these methods. Color formation also tends tobe suppressed under these conditions, resulting in polymers offavorable, off-white color.

However, the amount of phosphoric or polyphosphoric catalyst requiredfor optimal reaction by this method can be very high. It is probablethat the large quantities are needed to maintain acidic conditions inthe reaction, preventing thermal decomposition of amino termini, whichleads to chain termination. In addition, the hygroscopic phosphoric acidprobably serves to remove water, a byproduct of the condensationreaction, thus promoting the reaction. Upon continued heating, thiscaptured water could be vacated to the atmosphere (or the vapor space inthe reactor), restoring the hygroscopic tendency of the phosphoriccompound.

Later improvements in conjunction with this approach have included atwo-stage reaction, in which an intermediate product is mechanicallycommunited, followed by further condensation (Knebel et al., 1992, U.S.Pat. No. 5,141,062); addition of processing aids such as zeolites,sulfates, and bisulfates (Adler et al., 1995, U.S. Pat. No. 5,457,176);use of solvents such as diphenyl ether for azeotropic dehydration(Nagatomo et al. 1996, U.S. Pat. No. 5,484,945); addition of surfactantsto further disperse and promote mixing of the reactants, intermediates,and products (Chou, 1999, U.S. Pat. No. 5,856,427); the use of superpolyphosphoric acid (Tang, 1999, U.S. Pat. No. 5,929,198), and the useof cyclic propylene carbonate as a solvent (Mazo et al., 2001, U.S. Pat.No. 6,197,897). Knebel et al., cited above, reported non-crosslinkedpolysuccinimides having molecular weights greater than 100,000, using aprocess that requires interrupting polymerization, grinding(comminuting) a solid intermediate, and then continuing thepolymerization. The molecular weights were determined by viscometricmeasurements, which tend to give higher values than gel permeationchromatography (GPC) measurements. Morphology of the products (i.e.linear or branched) was not reported

Uenaka et al. (1997, EP 0791616 A1) employed triphenyl phosphite ortributyl phosphite as catalysts, along with organic solvents includingacetone, mesitylene, and sulfolane. These authors reported production ofpolysuccinimides up to Mw 75,000.

Irizato et al. (2001, JP 2001302794 A2) taught a modification oftraditional phosphoric acid catalyzed thermal polymerization of asparticacid, in which a fluid mixture of aspartic acid in water, methanol,ethanol, or a combination of these solvents, along with the phosphoriccatalyst, is formed. The mixture is atomized and spray-dried andsimultaneously thermally polymerized. The polysuccinimides so producedwere reported to range in Mw from 3,000 to 200,000.

Other approaches to generating polysuccinimides of higher Mw haveemployed various non-phosphoric acid catalysts. For example, gaseouscarbon dioxide, which purges the reactor to carry away the water ofcondensation and also provides a mildly acidic environment, has beenused to increase the Mw of product polysuccinimides (Kalota and Martin,1994, U.S. Pat. No. 5,329,020). There is also a report of the use ofbenzene sulfonic acid as a catalyst during thermal production of higherMw polysuccinimides (Wang, 2000, CN patent 1267673). In relatedapproaches, Kato et al. (1999, 2000) polymerized aspartic acid in thepresence of substoichiometric amounts of gaseous or aqueous HCl. If, inaddition, an aprotic solvent was used (JP 11-240947 A2), these authorsreported production of polysuccinimides up to Mw 60,000. In the absenceof solvents, in other words by use of aqueous or gaseous HCl alone toprovide acidic conditions, the Mw of the product polysuccinimides wasreported to range up to 30,000 (JP 2000-169577 A2).

Other non-phosphoric methods have included the use of sulfur-containingdehydration agents during thermal polymerization, resulting in somehigher Mw polysuccinimides of excellent light color (Batzel et al.,1996, U.S. Pat. No. 5,508,434). Another method employed mildcrosslinking, sufficient to increase Mw, but insufficient toinsolubilize the product polyaspartates that are produced frompolysuccinimide via the aqueous, ring-opening procedure (Ross et al.,1996, U.S. Pat. No. 5,552,516).

In actual practice, prior art methods have generally producedpolysuccinimides that range from about 10,000 to 30,000 in Mw, asmeasured by gel permeation chromatography (GPC) techniques. In addition,most studies have not addressed the molecular morphology of theproducts. Accordingly, there remains a need for a simple process forforming very high molecular weight, low color, substantially linearpolysuccinimides.

SUMMARY OF THE INVENTION

In one aspect, the invention provides a method of preparingpolysuccinimide by polymerization of aspartic acid. The method comprisesthe steps of

(a) forming a solution of aspartic acid and a water solublepolymerization catalyst in an aqueous medium containing a volatileprotic acid selected from the group consisting of hydrochloric acid,hydrobromic acid, and hydroiodic acid;

(b) drying the solution to give a solid residue; and

(c) heating the residue at a temperature and for an amount of timesufficient to produce a polysuccinimide polymer.

In one embodiment, the protic acid is hydrochloric acid Thepolymerization catalyst is preferably an acidic, hygroscopic compound,preferably selected from the group consisting of phosphoric acid(orthophosphoric acid), a polyphosphoric acid, phosphorus pentoxide, andcombinations thereof.

In carrying out the process, the catalyst is preferably present in theaqueous solution in an amount between about 5% to 50% by weight, morepreferably between about 20% to 30% by weight, of the amount of asparticacid. The molar ratio of the protic acid (i.e. HCl, HBr, or Hl) toaspartic acid in the solution is between about 1.0 and about 1.5. Thedrying step (b) is preferably carried out at a temperature between about60° C. and about 160° C., and the heating step (c) is preferably carriedout at a temperature between about 150° C. and about 350° C., and morepreferably between about 180° C. and about 240° C.

In selected embodiments, the heating step (c) is carried out at atemperature and for an amount of time sufficient to produce apolysuccinimide polymer having a weight average molecular weight greaterthan 30,000, greater than 60,000, or greater than 100,000.

In another aspect, the invention provides a polysuccinimide polymerproduced by process outlined in steps (a)-(c) above. In selectedembodiments, the polymer has a weight average molecular weight greaterthan 100,000; in another embodiment, greater than 150,000. Preferably,the polymer has a substantially linear morphology, such that a branchpoint occurs fewer than once every 8 residues. In one embodiment, such apolymer has a weight average molecular weight greater than 100,000. Infurther preferred embodiments, the polymers are off-white to white incolor.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with the invention, very high molecular weightpolysuccinimides can be prepared via a process in which the asparticacid monomer is initially solubilized and combined, in solution, with anacidic, hygroscopic agent which functions as a catalyst in thepolymerization reaction. The catalyst may be added to the solubilizedmonomer, or it may be added concurrently with the solubilizing agent,described below, or prior to the solubilization step. The solubilizationof the monomer as described herein allows more intimate contact betweenthe monomer and acidic catalyst upon drying of the reaction mixture,prior to polymerization. The polymers can have molecular weights up to200,000 daltons or more, as determined by GPC (gel permeationchromatography), e.g. as described in “Materials and Methods” below.

A. Solubilization of Aspartic Acid Monomer

Commercial aspartic acid is available as a crystalline zwitterionicmaterial, as shown below. The zwitterion is precipitated from the mildlyalkaline ammonium aspartate solutions that are formed during thecommercial synthesis of aspartic acid via enzymatic conversion ofammonium fumarate to ammonium aspartate. To produce the solid product,the solution is acidified to promote precipitation of the aspartic acidcrystals. When the pH reaches the isoelectric point at slightly lessthan pH 3, the β-carboxyl group is fully neutralized to the carboxylicacid form (pK_(a)˜3.9) while the (X-carboxyl group remains in theanionic carboxylate form (pK_(a)˜2.1). The amine group is fullyassociated as the cationic NH₃ ⁺ (pK˜9.8).

In this form, the crystals are quite insoluble in water, even withheating. They can be solubilized via addition of alkali to a slurry inwater, producing an aqueous solution of sodium (or other cation)aspartate. However, thermal polymerization of this product isunsuccessful, as the sodium counterions block the carboxylate groupsfrom forming amide bonds with the amine groups.

Aspartic acid is also soluble in relatively strong acids. For example,sulfuric or nitric acids, added in equimolar amounts or in slightexcess, will quickly bring aspartic acid into aqueous solution,particularly with mild heating. In these solutions, the aspartic acid isfully acidified, with both of the carboxylic groups in the acidic COOHform and the amine positively charged as NH₃ ⁺. In the absence ofcounterionic COO⁻ groups, no crystal lattice is formed.

Upon drying of such a solution, however, the anionic counterions (e.g.sulfate or nitrate) remain to block the amine groups, making themunavailable for amide formation with the unblocked carboxylic groups.This is the converse of the above-mentioned cationic blocking of thecarboxylate groups, and therefore again is not an acceptable situationfor successful thermal polymerization.

Consequently, the preferred solubilizing agents, either acidic or basic,are those which do not leave blocking counterions as components of thedried composition. The preferred solubilizing acid is a volatile acid,such as hydrochloric acid (bp −85° C.), hydrobromic acid (bp −67° C.),or hydroiodic acid (bp −35° C.), where hydrochloric acid is preferred.Upon dissolution in water, the gas (e.g. HCl) strongly dissociates asthe acid; upon drying, the gas vents to the atmosphere, leaving noresidue, and reducing acidity by forcing the reaction to the left:↑HCl+H₂O=H⁺+Cl⁻+H₂O.

Preferably, a small molar excess of acid, e.g. HCl, is employed relativeto aspartic acid in the dissolution process, producing a mildly acidicsolution which can be safely employed in commercial settings, providedthe acid is properly metered into the aspartic acid slurry and thenrecaptured upon drying of the intimate mixture of aspartic acid crystalsand catalyst.

An analogous alkaline solubilizing agent is ammonia, also a smallneutral gas. When dissolved in water, it strongly associates to producethe alkaline solution of ammonium hydroxide. Upon drying, again the gasvents to the atmosphere, leaving no residue, and reducing alkalinityconditions by forcing the reaction to the left:↑NH₃+H₂O=NH₄ ⁺+OH⁻+H₂O.

However, because a mildly alkaline solution is formed in this case, someportion of the acidic reaction catalyst (typically phosphoric acid) willbe converted to dihydrogen phosphate (H₃PO₄=H⁺+H₂PO₄ ⁻). On drying toform the intimate mixture of aspartic acid and catalyst, any excessdihydrogen phosphate anions can ionically block the cationic NH₃ ⁺groups of the aspartic molecules and prevent amide formation of thepolyamino acid backbone, in the manner described above.

Accordingly, the use of an aqueous solution of a volatile acid is thepreferred solubilization method. Preferably, for each mole of asparticacid to be dissolved, about 0.5 to 1.5 moles of acid, preferably HCl, isemployed A molar excess of HCl can be used to expedite dissolution. Mostpreferably, a small excess of HCl is used; e.g. about 1.2-1.3 mole ofHCl per mole of aspartic acid

The concentration of aspartic acid in the aqueous solution preferablyranges from 1% to 60% by weight, more preferably 10% to 50 by weight,most preferably 20 to 40% by weight.

Another aspartic acid solubilization method that does not suffer fromthe drawback of blocking counterions, as described above, is the use ofelectrolysis of water to generate the H⁺ ions needed to solubilize theaspartic acid zwitterionic crystals. In this modification, a smallequimolar excess (similar to the molar ratios described above) ofhydrogen ion relative to aspartic acid monomer is generatedelectrolytically, by use of commercial electrodialysis units, into acompartment that contains the aspartic acid crystals in aqueoussuspension. A solution forms, which is then pumped to a vessel intowhich the catalyst is metered.

B. Acidic Catalyst

Prior to, concurrent with, or preferably, following solubilization ofthe monomer as described above, an acidic catalyst, which preferablyalso functions as a hygroscopic agent, is added, to produce an acidicreaction mixture.

Typically, the catalyst is a phosphorus-containing acid, such asphosphoric acid (H₃PO₄, also known as orthophosphoric acid),metaphosphoric acid, diphosphoric acid (also known as pyrophosphoricacid), or polyphosphoric acid, which is provided commercially (e.g. byAldrich) as a mixture of tri- and higher phosphoric acids. Any of thesemay also be used in combination with each other or with phosphoruspentoxide. A catalyst known as super polyphosphoric acid comprises acombination of polyphosphoric acid and phosphorus pentoxide (see Tang,cited above). Other acidic catalysts have also been used in asparticacid polymerization, including acidic ion exchange resins (Jacquet etal., U.S. Pat. No. 4,363,797), CO₂ (Kalota et al., cited above) andbenzene sulfonic acid (Wang, cited above). Other acidic, hygroscopiccompounds that may be employed as catalysts include triphenyl ortrialkyl phosphites, e.g. tributyl phosphite (Uenaka et al. 1997, EP0791616 A1), sulfonic acids, e.g. benzenesulfonic acid, toluenesulfonicacid, or methyl sulfonic acid (Wang, 2000, CN patent 1267673), and othersulfur compounds, including sulfur trioxide, sulfuric acid, fumingsulfuric acid, sulfamic acid, polysulfuric acid, and salts thereof(Batzel et al., 1996, U.S. Pat. No. 5,508,434). In general, anyeffective acidic catalyst, preferably a hygroscopic catalyst, can beused in the methods described herein. Preferably, phosphoric orpolyphosphoric acid is used; most preferably, polyphosphoric acid isused.

The catalyst is dissolved in the solution of aspartic acid in an amountrelative to aspartic acid which is preferably 1% to 150% by weight, morepreferably 5% to 50% by weight, and most preferably 20% to 30% byweight. As shown below, increasing the amount of catalyst from 10% to20% to 30% produced a corresponding increase in the molecular weight ofthe product polymer. Molecular weights can also be varied by variationin reaction temperature and time of the final polymerization step,described below.

The solubilization produces a homogenous aqueous solution (that is,having no substantial amount of undissolved components) containingaspartic acid, the volatile dissolved acid, the polymerizationcatalyst(s), and water. Preferably, no other components are present inany significant amount; in particular, no organic solvents are required.

C. Drying

The combined solution of aspartic acid and catalyst is then dried, toremove water and more volatile components, e.g. HCl or other acid gas,to give a substantially solid residue. Drying is carried out, forexample, by heating at about 60-160° C., preferably about 80-1 40° C.,and more preferably at about 120° C., for a sufficient time to produce adried intimate mixture of monomer and catalyst. Evolved HCl or other gasmay be trapped, e.g. by use of a water trap, if needed.

Drying techniques include those known in the art, such as sparging withhot air, forced-air convection, spray drying, rotary evaporation, vacuumdrying, or thin layer convection. Preferred methods include forced-airconvection and spray drying. Upon drying, an intimate composition ofaspartic acid plus catalyst is produced.

D. Polymerization

The residue from the above drying process is then thermally polymerized,to produce polysuccinimides of Mw up to 200,000 and higher.Polymerization may be carried out by heating in conventional commercialconvection ovens, vacuum ovens, tray driers, or high-viscosity reactorssuch as extruders and co-rotating processors, using forced air or vacuumto carry away the vapors of condensation bond formation and other vaporsthat may occur. Preferably, high viscosity reactors and tray driers areused. Most preferably, high viscosity reactors are used.

The temperature of thermal polycondensation is preferably between about150-350° C., more preferably between about 170-240° C., and mostpreferably between about 180-200° C. The time of the polymerizationreaction preferably ranges between about 3 minutes, for the highestrange of temperatures, to 24 hours, for the lower temperatures. Morepreferably, the time of polymerization ranges between about 20 minutesand 6 hours, and most preferably, between about 30 minutes and 2 hours.

The above-described methods can be used to produce polysuccinimideshaving weight average molecular weights up to about 200,000 or higher,as shown in the Examples below, and also having excellent light colorand substantially linear morphology. Desired molecular weights can beobtained by variation in reaction temperature and time.

The products are readily purified of catalyst by successive washingswith water, each washing followed by filtration or centrifugation. Thepolymers may be further purified and dried, if desired, by techniquesknown in the art, such as dialysis with drying by lyophilization.

EXAMPLES

The following Examples serve to illustrate but not to limit theinvention.

Materials and Methods.

Conversion of the polysuccinimides to the corresponding polyaspartates.The polysuccinimides were ring-opened via mild alkaline hydrolysis byaddition of 1 equivalent of NaOH per equivalent of succinimide residuesto slurries of the polymers in water. The polymers were weighed, thenadded to beakers containing distilled water, with smooth magneticstirring. The alkaline conditions were held at pH 10 by autotitration ormanual pipetting, with the temperature at 80° C. as set by use of athermostated water bath. Typically, under these mild conditions, thepolysuccinimides were converted to the polyaspartates withinapproximately 1 hour.

Molecular weight. The molecular weights of the polyaspartates weredetermined by gel permeation chromatography (GPC), with commercialpolyaspartates and polyacrylates as standards. In addition, themolecular weights of specific copolymers were measured by massspectroscopy (matrix-assisted, laser desorption (MALDI MS) withtime-of-flight detector), and then used themselves as standards for GPCdeterminations.

Color. The color of the polysuccinimides and their correspondingpolyaspartates, both as solids and aqueous solutions, was assessed byvisual comparison to color standards (ASTM) available from commercialsources. In addition, the ultraviolet and visible light spectra ofstandard aqueous solutions of the copolymers were compared to indicatethe intensity of color development at particular wavelengths.

Molecular morphology. Branching versus linearity of the polyaspartateswas assessed in two ways. The first employed an advanced method inatomic force microscopy. The second utilized quantitative titration ofthe C-terminal, carboxylic end-groups of polysuccinimide molecules. Thenumber of end groups as compared to the known molecular weight of themolecules can provide an indication of the number of branches, as eachbranch has an end group.

Atomic force microscopy.. First, a novel method of atomic forcemicroscopy (AFM) was used to visually inspect the appearance of themolecules at the nanometer and angstrom levels. The method involvedfirst immobilizing the polymers at the surfaces of calcite crystals byallowing the polymers to embed themselves partially at growing crystalsurfaces by placement of functional groups of the polymers into latticepositions of the crystal surface. The polymers, so immobilized and heldtightly to an atomically flat surface, were then imaged via contact-modeAFM in solution. The visually evident differences between branchedversus unbranched molecules were clear.

Infrared spectroscopy. The infrared spectra of polysuccinimides andpolyaspartates were determined by use of conventional IRspectrophotometers equipped with attenuated total reflectance. Thespectra revealed the characteristic imide and amide peaks, thusindicating the occurrence of succinimide and aspartate residues.

Titration. Quantitative alkalimetric titrations of the polysuccinimidesover the pH range of 2.5 to 7.0 were made by use of an automatedtitrator. The amount of alkali that was consumed over this rangeindicated the amount of titratable groups of aspartic acid per unitweight of the polymers.

Amino acid analysis. The polyaspartates were hydrolyzed via acidtreatment to produce the monomeric constituents. These were then treatedto form their phenylthiohydantoin derivatives by use ofphenylisothiocyanate. The derivatized residues were next assessed viareverse-phase, liquid chromatography and identified by comparison tochromatograms of standards of the amino acids, also so treated. Thismethod generated quantitative data of the amount of aspartic acidresidues per unit weight of the polymers. This provided an indication ofthe relative amount of non-aspartic residues in the polymers, such asmight occur as end groups due to thermal decomposition of the aminotermini.

Example 1 Polyphosphoric Catalysis of Synthesis of Polysuccinimides viaThermal Polycondensation of HCl-Solubilized Aspartic Acid

Amounts of 0.01 mole of L-aspartic acid (1.33 g) were added to each of aset of 50-ml beakers. The aspartic acid (zwitterionic form, SigmaChemical) was dissolved in 13.3 ml of 1 N HCl (1 mmol per ml, total of0.013 mole, Fisher Chemical), at room temperature with smooth magneticstirring.

To 3 of these beakers was added 10% by weight of the aspartic acid aspolyphosphoric acid. This was added by pipetting 0.133 g or 0.066 ml ofpolyphosphoric acid (Aldrich Chemical, specific gravity˜2.0) into eachbeaker, first warming both the polyphosphoric acid and the pipette to80° C. to render the acid much less viscous and more easily pipettable.

To another 3 of the beakers was added 20% by weight of the aspartic acidas polyphosphoric acid. This was added by pipetting 0.266 g ofpolyphosphoric acid as above.

To the last 5 of the beakers was added 30% by weight of the asparticacid as polyphosphoric acid. This was added as above by pipetting 0.399g of polyphosphoric acid.

The solutions of aspartic acid plus polyphosphoric acid were dried at120 ° C. overnight in a small, conventional convection oven placed in afume hood This resulted in clear, glassy pucks of intimate mixtures ofaspartic acid and the catalyst.

These dried intimate mixtures were next thermally polymerized at 180° C.in the beakers in the same oven. Samples (as 1 beaker from eachtreatment) were taken from 1 to 7 hours of heating for each of thelevels of catalyst, 10, 20, and 30% by weight.

The resulting polysuccinimides were washed of the catalyst by stirringwith distilled water, centriftiging (3000 g for 10 minutes), thistreatment repeated 3 times. Each sample was then lyophilized to producea light powder.

The polysuccinimides were next ring-opened to produce stock solutions ofsodium polyaspartates via mild alkaline hydrolysis. These stocksolutions were used for determination of molecular weight via gelpermeation chromatography.

Example 2 Phosphoric-Acid Catalysis of Synthesis of Polysuccinimides viaThermal Polycondensation of HCl-Solubilized Aspartic Acid

The procedures and methods of Example 1 were followed except for use ofphosphoric acid (15% by weight water, 85% phosphoric acid, AldrichChemical) rather than polyphosphoric acid. Thus, for the 10% by weighttreatments, 0.156 g of the reagent (0.133 g as phosphoric acid) or 0.093ml (specific gravity 1.685) was pipetted. Accordingly, 0.313 g (0.266 g,0.186 ml) for the 20% by weight treatments, and 0.470 g (0.399 g, 0.279ml) for the 30% by weight treatments were pipetted.

The visual appearance and molecular weights of the product polymers weresimilar to those of Example 1, as exemplified in Table 1.

Comparative Example 1 Phosphoric Acid and Polyphosphoric Acid CatalyzedSynthesis of Polysuccinimides, via Thermal Polycondensation ofZwitterionic Aspartic Acid, not Solubilized

The amounts of phosphoric acid and aspartic acid as indicated in example2 were used, but the aspartic acid was not solubilized. Rather, a pasteof the aspartic acid (zwitterionic) and the catalyst was made bythoroughly mixing them manually by use of a spatula, the mixture havingbeen warmed to 80° C. by use of a thermostated heating plate. The pastewas then thermally polymerized at 190° C. The optimal reaction timeunder these conditions was 4.5 to 6 hours. The maximum molecular weightof polysuccinimide that was produced was approximately 30,000 daltons.If the amounts of the catalyst were increased to >30% by weight of theaspartic acid, the molecular weights of the resulting polysuccinimideswere decreased into the range of 10,000 daltons. Similar results wereobtained when polyphosphoric acid was used to make the paste withaspartic acid, zwitterionic monomer.

Comparative Example 2 Phosphoric Acid Catalyzed Synthesis ofPolysuccinimides via Thermal Polycondensation of Zwitterionic AsparticAcid, Solubilized by Addition of NaOH

The aspartic acid was readily brought into solution by titration withNaOH to produce a clear, aqueous solution at pH 5. To solutions of thistype were pipetted the various amounts of phosphoric acid as indicatedin example 2. Upon addition of the phosphoric acid at levels above 15%by dry weight of the aspartic acid, a large amount of precipitate of thecontents of the solution formed. Thus the addition of phosphoric acid inthis treatment was limited to 15%.

Following drying, the intimate mixture was thermally polymerized.Polyaspartates of very low molecular weight (less than 2,000 daltons)were produced. Polysuccinimides were not produced, as shown by the lackof the imide signal in the infrared spectra, owing to the presence ofsodium cations that blocked the ring-closure to form the imide residues.

Comparative Example 3 Phosphoric Acid Catalyzed Synthesis ofPolysuccinimides via Thermal Polycondensation of Zwitterionic AsparticAcid, Solubilized by Addition of NH₄OH

The protocol as described in comparative example 2 was followed with theaddition of phosphoric acid in the amount of 15% by weight of theaspartic acid In this case, however, the aspartic acid was firstsolubilized by addition of ammonium hydroxide to produce a clearsolution of aspartic acid at pH 5. Again a precipitate occurred uponaddition of the phosphoric acid at levels above 15% by dry weight of theaspartic acid In these experiments, no sodium counterions were presentto block imide formation, and the products formed were polysuccinimidesas indicated by the infrared spectra. However, again, the molecularweights were quite low, presumably now due to blockage of free R—NH₃ ⁺groups by the anionic dihydrogen phosphate anions (pK_(a)=2.1;H₃PO₄=H₂PO₄ ⁻+H⁺) in the dry intimate mixture prior to polymerization.

Comparative Example 4 Thermal Polymerization of Aspartic Acid, notSolubilized, with No Catalyst, 180° C.

Amounts of 0.01 mole of L-aspartic acid (1.33 g, zwitterionic form,Sigma Chemical) were added as the dry powders to each of a set of 50-mlbeakers. These were then placed in a convection oven at 180° C. andpolymerized for 2 to 24 hours. The resulting products were mixtures ofunreacted monomer, oligomers, and polysuccinimides. The temperature inthis case was too low to effectively condense the monomer to thepolymeric form in high yield, even after 24 hours of the thermaltreatment.

Comparative Example 5 Thermal Polymerization of Aspartic Acid, notSolubilized, No Catalysis, 220° C.

The procedure of comparative example 4 was followed The resultingproducts after about 4 hours of heating were almost fully converted tothe polysuccinimides. The polysuccinimides were ring-opened by mildalkaline treatment to produce sodium polyaspartates, which were thenassessed for Mw by gel permeation. These polyaspartates were relativelysmall, in the range of 3,000 to 5,000 Daltons.

Comparative Example 6 Thermal Polymerization of HCl-Solubilized AsparticAcid, No Catalysis, 220° C.

The procedure of example 1 was followed except that no phosphoriccatalyst was used. The aspartic acid was fully solubilized via thetreatment with HCl, but then was reprecipitated, presumably mainly asthe zwitterion, upon removal of HCl on drying. After 4 hours at 220° C.,the products were essentially fully converted to polysuccinimides. TheMw's of the resulting polyaspartates ranged from about 2-3 KDa TABLE 1Molecular weights of polyaspartates derived from polysuccinimidesproduced via conventional phosphoric acid catalysis and via HClsolubilization plus phosphoric acid catalysis Reaction Elution Time,Volume, hours ml at 1 Estimated Treatment at 180° C. ml/min Mw Example 1Aspartic acid 2 8.3 7,400 HCl solubilized, 4 8.1 12,000 10% polyphos 78.1 12,000 Aspartic acid 2 7.7 28,000 HCl solubilized, 4 7.6 33,000 20%polyphos 7 7.5 38,000 Aspartic acid 1 6.63 110,000 HCl solubilized, 26.48 122,000 30% polyphos 3 6.29 136,000 4 5.82 172,000 6 5.74 178,000Example 2 Aspartic acid 1 6.56 116,000 HCl solubilized, 2 6.40 128,00030% phosphoric 3 6.19 144,000 4 6.27 138,000 Comparative Aspartic acid 28.5 4,200 Example 1 not solubilized, 4 8.4 6,000 10% phosphoric 7 8.28,200 Aspartic acid 2 8.2 8,200 not solubilized, 4 8.1 12,000 20%phosphoric 7 8.0 16,000 Aspartic acid 2 8.0 16,000 not solubilized, 47.9 20,000 30% phosphoric 7 7.7 28,000 Comparative Aspartic acid, 4 8.8<2,000 Example 2 NaOH solubilized, 15% phosphoric Comparative Asparticacid, 4 8.8 <2,000 Example 3 NH₄OH solubilized, 15% phosphoricComparative Aspartic acid 4 Incomplete Not Example 4 Not solubilizedreaction applicable No catalyst, 180° C. Comparative Aspartic acid, 48.5 4,000 Example 5 Not solubilized, No catalyst, 220° C. ComparativeAspartic acid, 6 8.65 ˜2,000 Example 6 HCl-solubilized, No catalyst,220° C.

TABLE 2 Gel permeation standards for assessment of molecular weights ofthermal polymers of aspartic acid. Elution volume, Standard ml at 1ml/min Molecular weight ⁻O-(aspartate)₅-NH₃ ⁺ 9.2 593 solid-phasestandard Polyaspartate 8.6 2,300 Polyaspartate 8.4 6,000 Polyaspartate8.2 8,200 Polyaspartate 7.72 28,000 Polyglutamate 7.27 61,600Polyglutamate 6.96 86,000 Polyacrylate 4.9 1,000,000

1. A method of solubilizing aspartic acid crystals in an aqueoussuspension, to form an aqueous solution of aspartic acid, the methodcomprising: contacting said crystals in said suspension with asolubilizing agent which does not leave blocking counterions upon dryingof the resulting aqueous solution, wherein said solubilizing agent isselected from (i) a volatile acid, selected from hydrochloric acid,hydrobromic acid, and hydroiodic acid, and (ii) hydrogen ions generatedby electrolysis of water in said aqueous suspension.
 2. The method ofclaim 1, wherein said solubilizing agent comprises (ii) hydrogen ionsgenerated by electrolysis of water in said aqueous suspension.
 3. Themethod of claim 2, for use in preparing a polysuccinimide polymer,further comprising the steps of: contacting said aqueous solution withan acidic polymerization catalyst; drying the solution to give a solidresidue; and heating the residue at a temperature and for an amount oftime sufficient to produce a polysuccinimide polymer.
 4. The method ofclaim 3, wherein said acidic polymerization catalyst is selected fromthe group consisting of phosphoric acid, metaphosphoric acid,diphosphoric acid, polyphosphoric acid, and combinations thereof.
 5. Themethod of claim 4, wherein said catatlyst further comprises phosphoruspentoxide.
 6. The method of claim 3, wherein said acidic polymerizationcatalyst comprises an acidic ion exchange resin.